CYP1A2 Cytochrome P450 1A2
CYP1A2 is the enzyme that clears caffeine, and it also metabolises clozapine, olanzapine, theophylline and melatonin.
What does CYP1A2 do?
CYP1A2 is the enzyme that clears caffeine, and it also metabolises clozapine, olanzapine, theophylline and melatonin. Unlike most pharmacogenes, its activity is driven at least as much by environment as by genotype: smoking and cruciferous vegetables induce it, oral contraceptives and fluvoxamine inhibit it. The *1F variant makes the enzyme more inducible, which is why the same coffee affects a smoking *1F/*1F carrier and a non-smoking *1A/*1A carrier so differently.
What do the CYP1A2 metaboliser phenotypes mean?
Each person carries two CYP1A2 alleles. Each allele has a function and an activity score; the two scores are added and the total is mapped to a phenotype as follows.
| Phenotype | How it is assigned | What it means |
|---|---|---|
| Ultrarapid Metabolizer | activity score ≥ 2.5 (*1F/*1F) | Highly inducible enzyme: fast caffeine clearance, especially in smokers. |
| Normal Metabolizer | activity score 1.5 – 2 | Typical clearance. |
| Intermediate Metabolizer | activity score 1 | Reduced clearance; caffeine and clozapine linger longer. |
| Poor Metabolizer | activity score ≤ 0.5 | Markedly reduced clearance. |
Which CYP1A2 star alleles are there, and how common are they?
| Allele | Function | Activity score | Defining variants | Frequency (EUR / EAS / AFR / SAS / AMR) | Note |
|---|---|---|---|---|---|
| *1 | normal function | 1 | reference | 45.0% / 30.0% / 50.0% / 40.0% / 45.0% | Wild-type/reference allele. Normal CYP1A2 inducibility and baseline activity. |
| *1C | decreased function | 0.5 | rs2069514 -3860G>A (promoter) | 1.0% / 23.0% / 5.0% / 10.0% / 8.0% | Decreased function allele. Promoter variant reduces CYP1A2 transcription. Common in East Asian populations (~23%). Associated with slower caffeine metabolism. |
| *1F | increased function | 1.5 | rs762551 -163C>A (intron 1) | 55.0% / 70.0% / 45.0% / 55.0% / 50.0% | Increased inducibility allele. The A allele in intron 1 increases CYP1A2 induction by smoking, cruciferous vegetables, and charbroiled meat. Homozygous A/A carriers are 'rapid' caffeine metabolizers. Very common globally. |
| *1K | decreased function | 0.5 | rs2069514 -3860G>A (promoter) rs762551 -163C>A (intron 1) | 0.5% / 10.0% / 3.0% / 5.0% / 4.0% | Decreased function allele. Combination of *1C and *1F variants. The *1C promoter variant dominates, resulting in decreased function despite the *1F inducibility variant. More common in East Asian populations. |
Which drugs does CYP1A2 affect?
- Caffeine Stimulant CPIC level B
- CYP1A2 clears about 95% of caffeine. Fast, inducible metabolisers feel less effect and clear it before bedtime; slow metabolisers keep it in circulation for many hours, and some studies link slow metabolism plus heavy coffee to higher cardiovascular risk.
- Clozapine Atypical Antipsychotic CPIC level B
- Clozapine levels depend on CYP1A2 activity, and on smoking, which induces the enzyme. Starting or stopping smoking can move clozapine concentrations enough to cause relapse or toxicity.
- Theophylline Bronchodilator CPIC level B
- Theophylline has a narrow therapeutic window and is cleared by CYP1A2. Slow metabolism, enzyme inhibitors or stopping smoking can push levels into the toxic range.
- Melatonin Supplement / Hormone CPIC level C
- Exogenous melatonin is cleared by CYP1A2. Slow metabolisers have higher and longer exposure from the same dose, which shows up as next-day drowsiness.
Can a 23andMe or AncestryDNA file tell you your CYP1A2 type?
The inducibility variant *1F (rs762551) is on every major consumer chip. Because CYP1A2 activity depends heavily on smoking and diet, genotype alone predicts caffeine clearance less well than for other pharmacogenes.
Upload your 23andMe, AncestryDNA or WeGene raw file → · Ask G2: “What is my CYP1A2 metaboliser status and which of my medicines does it affect?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.